Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogen peroxide (H2O2) is an essential electron acceptor for thyroid peroxidase-catalyzed iodination and coupling reactions. In the presence of iodide, its production is a limiting step in thyroid hormone biosynthesis. Several studies have demonstrated that the thyroid particulate fraction contains a Ca2+- and NADPH- dependent H@O@ generator (NADPH-O2:oxidoreductase), the so- called thyroid NADPH-oxidase. It has recently been demonstrated that cellular H2O2 release is under the tonic control of TSH in primary cultures of dog thyrocytes. The present study evaluates the effect of TSH on the thyroid NADPH-oxidase and cytochrome c reductase activities, two enzymes believed to be involved on H2O2 generation in the thyroid gland. There was almost no detectable NADPH-dependent H2O2 generator in the membranes of cells grown for 18 h without TSH. But cells grown in the presence of TSH (0.1 mU/ml) had a CA2+- and NADPH-dependent H2O2-generating activity that increased up to the third day in culture, as did the cell iodide organification capacity. This increase was also partially blocked by 12-O-tetradecanoylphorbol 13-acetate and cycloheximide. Forskolin and 8-bromo-cAMP both reproduced the action of TSH on the Ca2+- and NADPH-dependent H2O2 generator. In contrast, the thyroid NADPH-cytochrome c reductase activity in particles from control cells was similar to that of TSH-treated cells and was unaffected by forskolin or 12-O-tetradecanoylphorbol 13-acetate. These results suggest that NADPH-cytochrome c reductase activity is not regulated by TSH and, thus, reinforce the idea that this enzyme is not involved in thyroid H2O2 generation. On the other hand, the Ca2+- and NADPH-dependent H2O2 generator, so-called thyroid NADPH- oxidase, is induced by TSH through the cAMP cascade. Thus, it seems to be another marker of thyroid differentiation, in addition to thyroperoxidase and thyroglobulin, and could play a key role in thyroid hormone production.
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PMID:The Ca2+- and reduced nicotinamide adenine dinucleotide phosphate-dependent hydrogen peroxide generating system is induced by thyrotropin in porcine thyroid cells. 860 67

A calcium and NAD(P)H-dependent H(2)O(2)-generating activity has been studied in paranodular thyroid tissues from four patients with cold thyroid nodules and from nine diffuse toxic goiters. H(2)O(2) generation was detected both in the particulate (P 3,000 g) and in the microsomal (P 100,000 g) fractions of paranodular tissue surrounding cold thyroid nodules (PN), with the same biochemical properties described for NADPH oxidase found in porcine and human thyroids. In PN tissues, the particulate NADPH oxidase activity (224 +/- 38 nmol H(2)O(2) x h(-1) x mg(-1) protein) was similar to that described for the porcine thyroid enzyme. However, no NADPH oxidase activity was detectable in the particulate fractions from eight diffuse toxic goiter patients treated with iodine before surgery; all but one also received propylthiouracil or methimazole in the preoperative period. Thyroid cytochrome c reductase (diffuse toxic goiters = 438 +/- 104 nmol NADP(+) x h(-1) x mg(-1) protein; PN = 78 +/- 10 nmol NADP(+) x h(-1) x mg(-1) protein) and thyroperoxidase (diffuse toxic goiters = 621 +/- 179 U x g(-1) protein; PN = 232 +/- 121 U x g(-1) protein) activities were unaffected by iodide. Thus, the human NADPH oxidase seems to be inhibited by iodinated compounds in vivo and probably is an enzyme involved in the Wolff-Chaikoff effect. Our findings reinforce the hypothesis that thyroid NADPH oxidase is responsible for the production of H(2)O(2) necessary for thyroid hormone biosynthesis.
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PMID:Ca(2+)/nicotinamide adenine dinucleotide phosphate-dependent H(2)O(2) generation is inhibited by iodide in human thyroids. 1154 71